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10
Selected Clinical Calculations
OBJECTIVES
Upon successful completion of this chapter, the student will be able to:
Calculate heparin doses from medication orders and standardized
protocols.
Utilize equianalgesic dose charts to determine appropriate doses of
narcotic analgesics based on previous narcotic use.
Calculate estimated creatinine clearance rates and apply in dose
determinations.
Calculate ideal body weight and adjusted body weight and apply in
dose determinations.
Calculate various cholesterol ratios and cholesterol reduction percent
from clinical laboratory data.
Convert blood serum chemistry values from mg/dL to mmol/L
(International System).
Heparin-Dosing Calculations
Heparin, also known as unfractionated heparin or UFH, is a heterogeneous
group of mucopolysaccharides that have anticoagulant properties. Heparin
slows clotting time. It is derived from the intestinal mucosa or other suitable
tissues of domestic animals (often porcine) used for food by humans. Salt
forms of heparin, such as heparin sodium, are standardized to contain 180
USP Heparin Units in each milligram. Heparin salts are administered as
sterile aqueous solutions by intravenous infusion, intermittent intravenous
injection, or deep subcutaneous injection for the prophylaxis and treatment
of venous thrombosis. The commercial preparations, available in single-use
syringes and multiple-dose vials, indicate on their labeling the number of
USP Heparin Units of activity contained per milliliter.
Although heparin is a treatment option for acute venous
thromboembolism, its use carries with it the risk of hemorrhage. Patients
especially at risk include elderly patients; postsurgical patients; patients with
a history of peptic ulcers, severe renal, or hepatic failure; and patients who
recently have taken other medications that affect blood clotting time.
1
When heparin sodium is administered in therapeutic amounts, its dosage
is adjusted according to the results of tests measuring the patient’s level of
blood coagulation, or activated partial thromboplastin time (aPTT). These
tests are performed before each intravenous injection and approximately
every 4 to 6 hours when administered by intravenous infusion or
subcutaneously. In general, the aPTT value should be maintained at 1.5 to 2
times the patient’s pretreatment aPTT value or, when the whole-blood
clotting time is evaluated, approximately 2.5 to 3 times the control value.1,
2
The dose varies depending on the circumstances. Bolus doses, given by
direct intravenous injection, may be followed by a heparin intravenous
infusion. For prevention of thromboembolism following surgery, patients
receive 5000 units given by deep subcutaneous injection 2 hours before
surgery and an additional 5000 units every 8 to 12 hours thereafter as
required. Heparin is also used to treat patients with active phlebitis or with
pulmonary emboli.
3
In pediatric use, the initial dose may be 50 units/kg by intravenous
infusion, followed by maintenance doses of 100 units/kg every 4 hours or
20,000 units/m2/24 hours, infused continuously.
3
Figure 10.1 presents a hospital form for an adult weight-based heparin
protocol. The form allows physicians’ orders for bolus doses, as well as
protocols for intravenous heparin infusions. The values given in this figure
may differ from heparin protocols at other institutions. Pharmacists must
follow those used within their institutions of practice.
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FIGURE 10.1 Example of hospital form for adult weight–based
heparin protocol. (Courtesy of Nina Morris, Southwestern
Oklahoma State University, Weatherford, OK.)
Low-molecular-weight heparins (LMWHs) are also used as antithrombotic
agents and are the agents of choice in treating deep vein thrombosis and
pulmonary embolus. The products currently on the market in the United
States are enoxaparin sodium (LOVENOX) and dalteparin sodium
(FRAGMIN). Heparin has a molecular weight ranging from 3000 to 30,000
daltons, whereas LMWHs are fragments of heparin with mean molecular
weights of 4000 to 6000 daltons.4 These shorter compounds may be
administered subcutaneously (rather than intravenously, as is heparin), they
interfere less with platelet function, and they generally have a more
predictable anticoagulant response that does not require monitoring of
clotting times.
Special considerations in heparin management
Heparin is a very useful but potentially dangerous agent. It is administered
only when necessary and with extreme caution. Hemorrhage is a distinct risk
with heparin use, requiring patients to be closely monitored. Pediatric
patients and seniors are among those who require particular care in dosing.
Heparin-dosing errors can result from miscommunication (as with the use of
the abbreviation “u” for units), from miscalculation of the appropriate dose,
or from the administration of a product of incorrect strength. To reduce the
likelihood of the latter, products are available in which the strengths are
made distinctive by use of stark color-coding and bold, tall-letter labeling.
Example calculations of heparin dosing
1. An intravenous infusion contained 20,000 units of heparin sodium in
1000 mL of D5W. The rate of infusion was set at 1600 units/h for a 160lb patient. Calculate (a) the concentration of heparin sodium in the
infusion, in units/mL; (b) the length of time the infusion would run, in
hours; and (c) the dose of heparin sodium administered to the patient,
on a unit/kg/min basis.
2. A patient weighing 80 kg was given an initial bolus dose of heparin and
a heparin drip for the first 6 hours. Using Figure 10.1, what was the
total amount of heparin administered in this period?
Bolus dose [80 units/kg]:
Heparin infusion [18 units/kg/h]:
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3. After 6 hours, the aPTT for the patient in example problem 2 is 102
seconds. Use Figure 10.1 to determine any changes necessary in this
patient’s heparin therapy, and calculate a new flow rate for the infusion
in mL/h using the standard heparin IV solution.
According to Figure 10.1, the infusion for a patient with an aPTT of
greater than 90 seconds should be stopped for 1 hour and then
decreased by 3 units/kg/h when resumed. The new infusion rate would
then be calculated as follows:
4. Heparin sodium may be administered to children by intermittent
intravenous infusion every 4 hours at doses ranging from 50 to 100
units/kg of body weight. Using an injection containing heparin, 5000
units/mL, calculate the daily dosage range, in milliliters, for a 50-lb
child.
5. The pediatric maintenance dose of heparin sodium is stated in the
literature as 20,000 units/m2/24 hours. Using the BSA nomogram in
Chapter 8, and a heparin sodium injection containing heparin sodium,
1000 units/mL, calculate the daily volume of injection to administer to a
25-lb child measuring 22 inches in height.
Example calculations of low-molecular-weight
heparin dosing
The recommended dose of dalteparin sodium (FRAGMIN) for patients
undergoing hip replacement surgery is 2500 international units within 2
hours before surgery, 2500 units 4 to 8 hours after surgery, and 5000 units
daily for 5 to 10 days, starting on the postoperative day. How many
milliliters from a vial containing 10,000 units/mL should be administered (a)
before surgery, (b) after surgery, and (c) the day following surgery?
a.
b. Same as (a) = 0.25 mL
c.
CASE IN POINT 10.1
A
A 198-lb hospitalized patient is placed on heparin therapy to treat a
pulmonary embolism. The patient requires a bolus injection followed by a
heparin infusion. The hospital follows the protocol shown in Figure 10.1.
The hospital pharmacist has heparin available for bolus doses
containing 5000 units/mL in 5-mL vials and heparin for intravenous
infusion in 250-mL infusion bags each containing 25,000 units of heparin.
a. How many milliliters of the 5000 units/mL injection should the
pharmacist recommend as a bolus dose?
b. How many milliliters per hour of the heparin infusion should the
pharmacist instruct the nurse to deliver, based on the standard
infusion protocol?
c. If the intravenous set is programmed to deliver 60 drops per
milliliter, what should be the flow rate, in drops per minute, to
deliver the mL/h required in answer (b)?
d. How long will the 250-mL infusion bag last, in hours?
a
Case in Point courtesy of Flynn Warren, Bishop, GA.
Use of Equianalgesic Dosing Charts
Narcotic analgesics, also termed opioid analgesics, are widely prescribed to
relieve moderate to severe pain. They are used in cases of acute pain, such as
due to an injury or surgery, and in cases of chronic pain due to cancer,
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musculoskeletal conditions, and other illnesses. In cases of chronic pain,
when the patient will most likely receive a narcotic analgesic for an extended
period of time, the goal of therapy is usually to relieve the patient’s pain
enough that he or she can continue a normal lifestyle but without
overmedicating the patient and causing unwanted side effects of constant
drowsiness, lethargy, and constipation. Once a patient is established on a
chronic narcotic analgesic therapy, changes often have to be made to manage
the patient’s pain without overly sedating the patient. Furthermore, the
patient may be switched to a different narcotic analgesic medication if he or
she has developed a tolerance to the current medication regimen, cannot
tolerate the adverse effects of the current medication, or desires a more
convenient formulation or dosing schedule. In these cases, an equianalgesic
dosing chart, such as in Table 10.1, is used to determine the appropriate dose
of the new medication to ensure that the patient receives adequate pain relief
with minimal adverse effects. An equianalgesic dosing chart is used to
estimate the dose of the new narcotic analgesic to be used, and the patient
should still be monitored for pain relief and presence of side effects. Most of
the published charts are limited to adult patients weighing greater than 50
kg, and recommend a reduced dosage for elderly patients and patients with
renal or hepatic insufficiency. In addition, clinicians may reduce the stated
equivalent dose due to the potential for incomplete cross-tolerance between
opioid analgesics. To use the equianalgesic dosing chart, the daily dose of
the current medication is determined from the dose and dosage regimen,
compared to the daily dose in the chart, and then converted to the dose and
dosage regimen for new medication.
TABLE 10.1 OPIOID ANALGESICS: APPROXIMATE
EQUIANALGESIC DOSES FOR ADULTS
a
a
Adapted from Facts & Comparisons eAnswers [book online]. Baltimore, MD: Wolters Kluwer
Clinical Drug Information; 2020.
Whereas Table 10.1 provides equianalgesic dosing for opioids acting as full
agonists at the mu opioid receptor, a different chart is utilized for opioid
analgesics with different pharmacological profiles (Table 10.2). These
include buprenorphine (a partial agonist at mu opioid receptors), nalbuphine
and butorphanol (opioid agonist–antagonists, which block mu receptors and
stimulate kappa opioid receptors), and pentazocine (an agonist at kappa
receptors and weakly block mu receptors). The dosing chart for these opioids
determines a dose equivalent to 10 mg of parenteral morphine. The clinician
may then use this morphine dose to convert to another opioid analgesic by
consulting the equianalgesic dosing chart in Table 10.1.
TABLE 10.2 OPIOID AGONIST–ANTAGONIST
ANALGESICS: APPROXIMATE EQUIANALGESIC DOSES
FOR ADULTS
a
a
Adapted from Facts & Comparisons eAnswers [book online]. Baltimore, MD: Wolters Kluwer
Clinical Drug Information; 2020.
Drug-specific conversion charts are available for certain opioid analgesics.
For example, Table 10.3 provides equivalent dosing for conversion from an
existing narcotic analgesic to the highly potent fentanyl transdermal system.
Table 10.4 lists ratios to guide conversion from hydrocodone, oxycodone,
methadone, or morphine to oxymorphone extended-release tablets. If a
patient is changing to or from one of these narcotic analgesic medications, it
is important for the clinician to consult these drug-specific charts to guide
accurate and appropriate dosing.
TABLE 10.3 FENTANYL TRANSDERMAL DOSAGE
CONVERSION GUIDELINESa,
b
a
Adapted from Lexicomp Lexi-Drugs [book online]. Baltimore, MD: Wolters Kluwer Clinical Drug
Information; 2020.
b
This table should not be used to convert fentanyl transdermal to other therapies because the
conversion to fentanyl transdermal is conservative. Use of this table for conversion to other analgesic
therapies can overestimate the dose of the new agent. Overdosage of the new analgesic agent is
possible.
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TABLE 10.4 CONVERSION FACTORS TO
OXYMORPHONE ER TABLETS
a
a
Adapted from Facts & Comparisons eAnswers [book online]. Baltimore, MD: Wolters Kluwer
Clinical Drug Information; 2020.
Example calculations using equianalgesic dosing
charts
1. A patient is taking NORCO 7.5-mg tablets containing 7.5 mg of
hydrocodone bitartrate and 325 mg of acetaminophen to manage his
chronic back pain. His current dosage is two tablets every 6 hours, but
his pain management doctor would like to switch him to
hydromorphone hydrochloride tablets to better alleviate his pain.
Hydromorphone hydrochloride tablets are available in strengths of 2, 4,
and 8 mg and should be administered every 4 to 6 hours. Determine the
dose of hydromorphone hydrochloride for this patient.
According to the chart in Table 10.1, 30 mg of hydrocodone is
equivalent to 7.5 mg of hydromorphone taken orally.
Because the patient is accustomed to taking the current medication
every 6 hours, this dosage regimen would probably be most effective
for him.
The patient should begin with hydromorphone hydrochloride 4-mg
tablets every 6 hours and be monitored for relief of pain symptoms as
well as for adverse effects.
2. CR is a 57-year-old male patient who is 6 feet 1 inch tall and weighs 212
lb. He is receiving a 20-mg intravenous injection of pentazocine lactate
every 4 hours to control his pain after an injury due to a motorcycle
accident. His physician wishes to switch him to an oral dose of
meperidine hydrochloride so that he can move into a rehabilitation
facility. What would be the equivalent dose of meperidine hydrochloride
for this patient?
According to Table 10.2, a 30-mg injection of pentazocine is equivalent
to a 10-mg injection of morphine; therefore, the amount of morphine
represented by a 20-mg injection of pentazocine can be calculated as:
According to Table 10.1, a 10-mg injection of morphine is equivalent to
300 mg of meperidine given orally. The oral dose of meperidine for this
patient can be calculated as:
The patient can take two 100-mg meperidine hydrochloride tablets
every 4 hours to manage his pain.
3. A cancer patient is taking one 20-mg oxycodone tablet q.i.d. to manage
her pain. (a) What is the total daily oxycodone dose for this patient? (b)
The patient’s pain management physician decides to switch her to
fentanyl transdermal patches. What strength of fentanyl patch should he
prescribe?
5
a.
b. According to Table 10.3, a patient receiving an oral oxycodone dose of
67.5 to 112 mg/day of oral oxycodone should begin with a 50 mcg/h
fentanyl patch.
4. A patient with a spinal injury is taking one 15-mg tablet of immediate-
release morphine sulfate every 4 hours for pain. His physician wants to
switch him to oxymorphone hydrochloride extended-release tablets to
better manage his pain, and reserve the immediate-release morphine
tablets for breakthrough pain. The oxymorphone hydrochloride
extended-release (ER) tablets should be given every 12 hours. Calculate
the appropriate dose for this patient.
First, the daily dose of morphine sulfate must be calculated:
According to Table 10.4, a conversion factor of 0.333 should be used to
convert an oral dose of morphine to oxymorphone ER tablets.
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